التفاصيل البيبلوغرافية
| العنوان: |
The ectonucleotidase CD39 identifies tumor-reactive CD8+ T cells predictive of immune checkpoint blockade efficacy in human lung cancer. |
| المؤلفون: |
Chow, Andrew1,2,3 (AUTHOR) chowa1@mskcc.org, Uddin, Fathema Z.1 (AUTHOR), Liu, Michael1 (AUTHOR), Dobrin, Anton1,4,5 (AUTHOR), Nabet, Barzin Y.6 (AUTHOR), Mangarin, Levi2 (AUTHOR), Lavin, Yonit1 (AUTHOR), Rizvi, Hira1,7 (AUTHOR), Tischfield, Sam E.8 (AUTHOR), Quintanal-Villalonga, Alvaro1 (AUTHOR), Chan, Joseph M.1 (AUTHOR), Shah, Nisargbhai1 (AUTHOR), Allaj, Viola1 (AUTHOR), Manoj, Parvathy1 (AUTHOR), Mattar, Marissa9 (AUTHOR), Meneses, Maximiliano9 (AUTHOR), Landau, Rebecca9 (AUTHOR), Ward, Mariana9 (AUTHOR), Kulick, Amanda9 (AUTHOR), Kwong, Charlene9 (AUTHOR) |
| المصدر: |
Immunity (10747613). Jan2023, Vol. 56 Issue 1, p93-93. 1p. |
| مصطلحات موضوعية: |
*T cells, *IMMUNE checkpoint proteins, *PROGRAMMED death-ligand 1, *LUNG cancer, *NON-small-cell lung carcinoma |
| مستخلص: |
Improved identification of anti-tumor T cells is needed to advance cancer immunotherapies. CD39 expression is a promising surrogate of tumor-reactive CD8+ T cells. Here, we comprehensively profiled CD39 expression in human lung cancer. CD39 expression enriched for CD8+ T cells with features of exhaustion, tumor reactivity, and clonal expansion. Flow cytometry of 440 lung cancer biospecimens revealed weak association between CD39+ CD8+ T cells and tumoral features, such as programmed death-ligand 1 (PD-L1), tumor mutation burden, and driver mutations. Immune checkpoint blockade (ICB), but not cytotoxic chemotherapy, increased intratumoral CD39+ CD8+ T cells. Higher baseline frequency of CD39+ CD8+ T cells conferred improved clinical outcomes from ICB therapy. Furthermore, a gene signature of CD39+ CD8+ T cells predicted benefit from ICB, but not chemotherapy, in a phase III clinical trial of non-small cell lung cancer. These findings highlight CD39 as a proxy of tumor-reactive CD8+ T cells in human lung cancer. • CD39+ CD8+ T cells express features of exhaustion and tumor reactivity • CD39 expression enriches for CD8+ TCRs with tumor reactivity • CD39 expression on CD8+ T cells is non-redundant to tumor-based biomarkers • CD39+ CD8+ T cells are predictive of benefit from ICB Factors predicting benefit of immune checkpoint blockade (ICB) are needed. Here, Chow et al. demonstrate that CD39 expression marks tumor-reactive CD8+ T cells. High baseline levels of CD39+ CD8+ T cells are associated with ICB efficacy in lung cancer. Thus, CD39 is a potential tumor-extrinsic biomarker for guiding cancer management. [ABSTRACT FROM AUTHOR] |
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